The proposed studies are designed to investigate the potential role of trophoblastic progesterone production in preventing maternal rejection of the products of conception. In vivo and in vitro experiments will be performed to identify the specific cells of the host defense mechanism that are affected during progesterone inhibition of the inflammatory response. Specifically, the mechanism by which estrogen promotes and progesterone inhibits eosinophil accumulation in the uterus will be studied. Direct effects on cells and hormone induced production of chemotactic factors will both be considered. The cellular events that occur at the uteroplacental junction following progesterone withdrawal will be studied in pregnant rats and rabbits. In other studies attempts will be made to induce growth of human trophoblastic cells in rats treated with pregnenolone in order to increase progesterone synthesis by the trophoblasts. Enzymatic activities responsible for progesterone synthesis by the human placenta will be studied at different stages of gestation. Regulators that may increase steroid 20 alpha-dehydrogenase will be studied in a superfusion system. Finally, the conversion of pregnenolone sulfate to progesterone in the placenta of pregnant sheep and monkeys will be studied to determine the feasibility of increasing endogenous progesterone production ultimately in humans.